Although the nicotinamide nucleotides NAD（H） and NADP（H） are essential for various metabolic reactions that play major roles in maintenance of cellular homeostasis, the significance of NAD biosynthesis is not well...Although the nicotinamide nucleotides NAD（H） and NADP（H） are essential for various metabolic reactions that play major roles in maintenance of cellular homeostasis, the significance of NAD biosynthesis is not well under- stood. Here, we investigated the dynamics of pollen nicotinamide nucleotides in response to imbibition, a representative germination cue. Metabolic analysis with capillary electrophoresis electrospray ionization mass spectrometry revealed that excess amount of NAD＊ is accumulated in freshly harvested dry pollen, whereas it dramatically decreased immedi- ately after contact with water, importantly, excess of NAD~ impaired pollen tube growth. Moreover, NAD~ accumulation was retained after pollen was imbibed in the presence of NAD^-consuming reaction inhibitors and pollen germination was greatly retarded. Pollen deficient in the nicotinate/nicotinamide mononucleotide adenyltransferase （NMNAT） gene, encoding a key enzyme in NAD biosynthesis, and a lack of NAD＊ accumulation in the gametophyte, showed precocious pollen tube germination inside the anther Iocule and vigorous tube growth under high-humidity conditions. Hence, the accumulation of excess NAD＊ is not essential for pollen germination, but instead participates in regulating the timing of germination onset. These results indicate that NAD＋ accumulation acts to negatively regulate germination and a decrease in NAD＋ plays an important role in metabolic state transition.展开更多
目的探讨烟酰胺腺嘌呤二核苷酸(NAD+)对脊髓缺血再灌注损伤(SCII)的保护作用。方法将24只大鼠按随机数字表法分为A组(不夹闭主动脉)、B组(主动脉夹闭后注射生理盐水)和C组(主动脉夹闭后注射NAD+)。采用大鼠脊髓损伤(BBB)评分评价神经功...目的探讨烟酰胺腺嘌呤二核苷酸(NAD+)对脊髓缺血再灌注损伤(SCII)的保护作用。方法将24只大鼠按随机数字表法分为A组(不夹闭主动脉)、B组(主动脉夹闭后注射生理盐水)和C组(主动脉夹闭后注射NAD+)。采用大鼠脊髓损伤(BBB)评分评价神经功能情况,尼氏染色了解脊髓前角正常运动神经元数目情况,测量脊髓组织中超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量来分析氧化应激情况,蛋白质免疫印迹测试脊髓中细胞凋亡情况。结果术后3、6、12、24、48 h BBB评分:B组和C组均低于A组(P<0.05),C组均高于B组(P<0.05)。尼氏染色显示一侧脊髓前角正常运动神经元数目:A组明显多于B组和C组(P<0.05),C组明显多于B组(P<0.05)。术后48 h SOD活性:B组和C组均低于A组(P<0.05),B组低于C组(P<0.05)。术后48 h MDA含量:B组和C组均高于A组(P<0.05),B组高于C组(P<0.05)。Cleaved Caspase-3蛋白表达水平:B组和C组均高于A组(P<0.05),B组高于C组(P<0.05)。结论NAD+通过减弱SCII后的氧化应激反应,保留脊髓前角的运动神经元,对脊髓缺血再灌注损伤起到神经保护作用。展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
SIRT1(Sirtuin type 1)是依赖NAD+的组蛋白去乙酰化酶,对作用底物组蛋白赖氨酸残基进行去乙酰化修饰而发挥多种生理功能.SIRT1通过增加脂肪分解,减少脂肪堆积;增加糖异生,维持正常血糖水平;增加胰岛素敏感性,改善胰岛素抵抗;抑制蛋白水...SIRT1(Sirtuin type 1)是依赖NAD+的组蛋白去乙酰化酶,对作用底物组蛋白赖氨酸残基进行去乙酰化修饰而发挥多种生理功能.SIRT1通过增加脂肪分解,减少脂肪堆积;增加糖异生,维持正常血糖水平;增加胰岛素敏感性,改善胰岛素抵抗;抑制蛋白水解酶活性,减少骨骼肌质量丢失等多种途径调节机体物质代谢,改善代谢的失衡.因此,提高SIRT1活性已成为治疗多种疾病的方法之一.运动是刺激SIRT1表达的有效因素,小分子多酚类是SIRT1的激活剂,低强度激光照射可改善SIRT1活性,这些方法均已广泛用于多种疾病的防治.展开更多
文摘Although the nicotinamide nucleotides NAD（H） and NADP（H） are essential for various metabolic reactions that play major roles in maintenance of cellular homeostasis, the significance of NAD biosynthesis is not well under- stood. Here, we investigated the dynamics of pollen nicotinamide nucleotides in response to imbibition, a representative germination cue. Metabolic analysis with capillary electrophoresis electrospray ionization mass spectrometry revealed that excess amount of NAD＊ is accumulated in freshly harvested dry pollen, whereas it dramatically decreased immedi- ately after contact with water, importantly, excess of NAD~ impaired pollen tube growth. Moreover, NAD~ accumulation was retained after pollen was imbibed in the presence of NAD^-consuming reaction inhibitors and pollen germination was greatly retarded. Pollen deficient in the nicotinate/nicotinamide mononucleotide adenyltransferase （NMNAT） gene, encoding a key enzyme in NAD biosynthesis, and a lack of NAD＊ accumulation in the gametophyte, showed precocious pollen tube germination inside the anther Iocule and vigorous tube growth under high-humidity conditions. Hence, the accumulation of excess NAD＊ is not essential for pollen germination, but instead participates in regulating the timing of germination onset. These results indicate that NAD＋ accumulation acts to negatively regulate germination and a decrease in NAD＋ plays an important role in metabolic state transition.
文摘目的探讨烟酰胺腺嘌呤二核苷酸(NAD+)在心肌缺血/再灌注中的作用及机制。方法 14只巴马小型猪随机分为2组(实验组,n=7,对照组,n=7),采用经皮球囊封堵冠状动脉建立心肌缺血/再灌注模型,再灌注前实验组给予20 mg/kg NAD(+)。再灌注后2 h及4周后分别行心肌核素显像记录心肌灌注总静息评分(summed rest score,SRS)及节段室壁运动距离。4周后行病理分析评估毛细血管密度。结果实验组心肌缺血程度较对照组轻(P=0.017),具有更低的SRS(P=0.036)。术后4周随访心功能,实验组心尖部缺血心肌,包括节段17(5.95±2.18)mm vs(1.66±1.90)mm,P=0.016,节段15(8.88±3.57)mm vs (3.68±2.97)mm,P=0.048),节段14(9.43±3.67)mm vs (1.90±1.73)mm,P=0.004)及节段13(5.28±2.72)mm vs (1.24±0.60)mm,P=0.014),较对照组运动能力更佳。此外,病理检测提示实验组较对照组微循环密度更高(1.16±0.38)%vs(0.83±0.54)%,P=0.019)。结论外源性补充NAD(+)通过促进血管生成,改善冠脉微循环,减少心肌缺血/再灌注损伤,改善心肌灌注及心功能。
文摘目的探讨烟酰胺腺嘌呤二核苷酸(NAD+)对脊髓缺血再灌注损伤(SCII)的保护作用。方法将24只大鼠按随机数字表法分为A组(不夹闭主动脉)、B组(主动脉夹闭后注射生理盐水)和C组(主动脉夹闭后注射NAD+)。采用大鼠脊髓损伤(BBB)评分评价神经功能情况,尼氏染色了解脊髓前角正常运动神经元数目情况,测量脊髓组织中超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量来分析氧化应激情况,蛋白质免疫印迹测试脊髓中细胞凋亡情况。结果术后3、6、12、24、48 h BBB评分:B组和C组均低于A组(P<0.05),C组均高于B组(P<0.05)。尼氏染色显示一侧脊髓前角正常运动神经元数目:A组明显多于B组和C组(P<0.05),C组明显多于B组(P<0.05)。术后48 h SOD活性:B组和C组均低于A组(P<0.05),B组低于C组(P<0.05)。术后48 h MDA含量:B组和C组均高于A组(P<0.05),B组高于C组(P<0.05)。Cleaved Caspase-3蛋白表达水平:B组和C组均高于A组(P<0.05),B组高于C组(P<0.05)。结论NAD+通过减弱SCII后的氧化应激反应,保留脊髓前角的运动神经元,对脊髓缺血再灌注损伤起到神经保护作用。
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
文摘SIRT1(Sirtuin type 1)是依赖NAD+的组蛋白去乙酰化酶,对作用底物组蛋白赖氨酸残基进行去乙酰化修饰而发挥多种生理功能.SIRT1通过增加脂肪分解,减少脂肪堆积;增加糖异生,维持正常血糖水平;增加胰岛素敏感性,改善胰岛素抵抗;抑制蛋白水解酶活性,减少骨骼肌质量丢失等多种途径调节机体物质代谢,改善代谢的失衡.因此,提高SIRT1活性已成为治疗多种疾病的方法之一.运动是刺激SIRT1表达的有效因素,小分子多酚类是SIRT1的激活剂,低强度激光照射可改善SIRT1活性,这些方法均已广泛用于多种疾病的防治.
